Abstract: A method is disclosed for automated multiplex sequencing of DNA with an integrated automated imaging hybridization chamber system. This system comprises an hybridization chamber device for mounting a membrane containing size-fractionated multiplex sequencing reaction products, apparatus for fluid delivery to the chamber device, imaging apparatus for light delivery to the membrane and image recording of fluorescence emanating from the membrane while in the chamber device, and programmable controller apparatus for controlling operation of the system. The multiplex reaction products are hybridized with a probe, then an enzyme (such as alkaline phosphatase) is bound to a binding moiety on the probe, and a fluorogenic substrate (such as a benzothiazole derivative) is introduced into the chamber device by the fluid delivery apparatus.

Abstract: The present invention provides an immunoassay method for screening for gram negative sepsis in a subject, in which the concentration of extracellular BPI in a plasma sample from the subject is determined and compared with a standard concentration of BPI indicative of gram negative sepsis.

Abstract: The present invention relates to the determination of thrombocytopenia induced by an inductor drug such as heparin. According to the invention, a sample is mixed with a complex of an antigenic substance such as platelet factor 4 (pF4) and heparin to determine if the sample contains antibodies which react with the complex. The presence of these antibodies is indicative of heparin-induced thrombocytopenia.

Abstract: The present invention provides a method for quantifying the presence of extracellular BPI in body fluids including blood in a subject comprising conducting a BPI immunoassay on plasma obtained from said subject.

Abstract: A magnetic separator for isolating magnetically-labeled substances of interest, such as immunological agents, from a non-magnetic test medium using a method of high gradient magnetic separation. The target substance is contacted with microscopic magnetic particles having a receptor for binding with the target substance. The test medium containing the magnetic particles is held in a non-magnetic container and placed into a gap within an arrangement of magnets for causing the magnetic particles to adhere to selected locations upon the interior wall of the container. The quantity of magnetic particles may be controlled to cause the magnetic particles collected upon the interior wall to form a monolayer. The magnets are arranged upon a yoke which may provide linear, surrounding multipolar, or partially surrounding multipolar configurations of magnetic pole faces about the gap.

Abstract: Immunoassay techniques for quantitating the amount of 3'-amido-3'-deoxythymidine (AMT) in body fluid samples, and antibodies useful in performing such immunoassays, are provided. The immunoassays use antibodies which are specific to AMT and have no cross-reactivity with 3'-azido-3'-deoxythymidine (AZT). Moreover, there is provided an improved method of conducting AZT therapy wherein the concentration of both AZT and AMT is monitored and the AZT dosage is adjusted to maintain rather low concentrations of AMT.

Abstract: The present invention concerns compounds having the general formula I ##STR1## in which R.sup.1 denotes hydrogen or hydroxy,R.sup.2 denotes hydrogen or hydroxy,R.sup.3 denotes hydrogen or alkoxy,R.sup.4 denotes hydrogen, CO.sub.2 H, SO.sub.3 H, PO.sub.3 H.sub.2 or a salt of the corresponding acid,R.sup.5 denotes CO.sub.2 H, SO.sub.3 H, PO.sub.3 H.sub.2 or a salt of the corresponding acid andR.sup.6 denotes alkoxy,their use for displacing iodothyronines from proteins binding them, as well as a method and reagent for the determination of iodothyronine in which such compounds are used.

Abstract: The signal generated in a specific binding assay wherein a peroxidase label is used to detect the resulting specific binding complex on a microporous filtration membrane can be modulated by contacting the signal forming reagents with a buffered solution of a hydroxamic acid or acyl hydrazine having the structureR--CO--NH--R'or an equivalent salt thereof, wherein R is aryl of 6 to 10 carbon atoms in the aromatic nucleus, alkyl of 1 to 7 carbon atoms or cycloalkyl of 5 to 10 carbon atoms in the ring, and R' is hydroxy or amino. This solution can be provided in a diagnostic test kit for use in various methods to detect a specific binding ligand. The result is improved signal stability and lowered background after the use of a high pH wash solution in the assay.

Abstract: Two hybridomas that produce receptors containing antibody combining sites that immunoreact with apolipoprotein B-100 are disclosed as are uses for the receptors, compositions and diagnostic systems that include the receptors.

Abstract: The present invention provides a storable POD conjugate solution, characterised by a pH value of 5.0 to 6.5, adjusted by means of an organic buffer substance with a concentration of 40 to 100 mmol/l, and 0.05 to 1.0 mol/l magnesium aspartate.

Abstract: Method of assay of enzymatic activity, including projecting excitation light to a sample containing an enzyme, a substrate which forms a product by action of the enzyme, and a reference substance which is insensitive to the action of the enzyme but emits fluorescence; obtaining a first measured value of fluorescence intensity of the sample at a first wavelength region which includes fluorescence emitted by the substrate or the product at least, obtaining a second measured value of fluorescence intensity at a second wavelength region which is different from the first wavelength region for the first measured value and includes fluorescence emitted by the reference substance; and assaying the enzymatic activity from the ratio of the first measured value to the second measured value and apparatus for performing the method. The method assures high accuracy and high sensitivity of measurement in enzyme labeled immunoassay and enzyme labeled DNA hybridization.

Abstract: The present invention relates to a novel monoclonal antibody reactive with human colorectal mucin antigen. More particularly, the antibody of the invention is a murine monoclonal antibody, CT43, reactive with a novel antigenic determinant on much antigen highly correlated with human colorectal cancer. The antigenic determinant found by the CT43 has been characterized as neuraminidase and proteinase K resistant, periodate sensitive and unreactive with the glycoconjugates of Table 2. Methods are provided for the detection and quantitation of the CT43 antigenic determinant and its correlation with colorectal cancer. CT43, and CT66 specific for the sialylated Lewis a and Lewis a antigen have been deposited with the American Type Culture Collection, as accession numbers ATCC HB 10217 and ATCC HB 10218, deposited Sep. 6, 1989.

Abstract: The invention relates to a method for assessing clinical activity and resistance to multiple anticancer drugs of mammalian cells, based on a dose-dependent inhibition with cytotoxic agents of the cellular rise in ornithine decarboxylase activity, following serum stimulation, which comprises the steps of: (a) determining by an immunological technique the rise in the ornithine decarboxylase protein levels, after adding serum containing medium to quiescent mammalian cells, and (b) obtaining the levels of the anticancer drug resistance from the ratio of 50% inhibitory concentration of ornithine decarboxylase obtained with an anticancer drug for drug resistant cells and drug sensitive cells. The immunological technique is selected from ELISA, radioimmunoassay, immunofluorescence, flow cytometry and fluorescence microscopy. The increase in the ornithine decarboxylase activity results from an increase in the number of ornithine decarboxylase molecules.

Abstract: The present invention relates to a method for early detection of lung cancer. The method comprises obtaining samples from the body, especially respiratory tract material including sputum or bronchial fluid or any other pulmonary tissue or thoracic cells or regional lymph nodes, and assaying the samples with monoclonal antibodies for the presence of antigens whose enhanced presence correlates with the development of lung cancer. The method of the present invention permits identification of lung cancer up to two years prior to the development of clinical lung cancer, and thus enables early treatment of the lung cancer.

Abstract: An assay provides for detecting the presence of an analyte in a sample. Sample is applied to move through three zones. A mobilizeable receptor capable of binding to the analyte is present in the first zone. A trap for unbound receptor, consisting of immobilized ligand, is present in the second zone. Receptor bound to analyte will not bind to the ligand; unbound receptor will bind to the ligand. Mobilization and migration of the receptor can be detected in the third zone, which positively indicates that analyte is present. A device for carrying out the method is also provided.

Abstract: The invention relates to a method of predicting disease-free survival in cancer patients by relating the number and amount of stress response proteins in cancer tissue to the probability of tumor recurrence. Particular heat shock/stress response proteins useful in the determination of tumor recurrence are the stress response proteins, hsp70, hsp90, hsp27, and glucose regulated protein grp94. Specific levels of the stress response proteins relative to an internal standard are identified, above which the probability of tumor recurrence is highly significant. Kit methods are disclosed which could enable determination of the stress proteins by an antibody assay.

Abstract: A first solution containing Tris-HCl, MgCl.sub.2, a homopolymer of 2-acrylamide-2-methylpropanesulfonate (AMPS) and agarose is applied to a filter having alkaline phosphatase to be detected. A second solution containing Tris-HCl, MgCl.sub.2, homopolymer of AMPS, 5-bromo-4-chloroindoxyl phosphate, nitroblue tetrazolium and agarose is applied onto a film formed by the first solution.

Abstract: Method for the immunological determination of a ligand in which the ligand to be determined is reacted witha) at least 2 molecules of a specifically bindable substance P2 of which at least one of these molecules carries a label andb) a receptor R which consists of a binding partner P1 which is capable of monovalent binding to P2 and a binding site R.sub.1 for the ligand to be determined and then the label is determined,as well as a reagent for the immunological determination of a ligand which contains a specifically bindable substance P2 which is present at least partially in labelled form and a receptor R which consists of a binding partner P1 which is capable of monovalent binding to P2 and a binding site R.sub.1 for the ligand to be determined.

Abstract: A method for carrying out a binding assay is described wherein a member of a specific binding pair (sbp) and a sample are combined with a matrix of non-porous beads in a liquid medium under conditions such that the beads bind to the sbp member. The liquid medium is removed from the beads by aspiration using an aspiration tube having one or more orifices each of a diameter smaller than the minimum diameter of the smallest bead thereby allowing removal of the liquid medium while prohibiting aspiration of the beads.

Abstract: A method of determining tenascin in a cerebrospinal fluid sample by immunoassay, etc. is disclosed. The tenascin level in the cerebrospinal fluid serves as a glioma marker and thus the selective diagnosis of glioma is possible.

Abstract: The present invention provides: a labelled .beta.-amyloid peptide of active fragment; a composition including the labelled .beta.-amyloid peptide or active fragment thereof and a pharmaceutical carrier; a method for labelling the .beta.-amyloid peptide or an active fragment thereof, and methods of using the labelled peptide or peptide fragment for detecting or monitoring Alzheimer's disease in a patient.

Abstract: Subject matter of the invention is a new method of detecting a substance with hydrolase activity in a sample, characterized in that the sample is brought into contact with an indicator enzyme, which is covalently bound to an insoluble carrier material and can be rendered soluble by the hydrolase activity, in that the cleaved off indicator is separated and in that its enzymatic activity is determined and test means for its implementation.

Abstract: A process for the detection of antibiotics in a liquid medium such as milk, urine and blood is disclosed which comprisesbringing together a fluid sample of the liquid medium, an labelled antibiotic binding protein, and an immobilized antibiotic,allowing the labelled antibiotic binding protein to bind with the immobilized antibiotic,removing labelled antibiotic binding protein which is not bound to immobilized antibiotic, anddetermining the amount of the labelled antibiotic binding protein bound to the immobilized antibiotic.

Abstract: Compounds are evaluated for their binding to naturally occurring receptors, by employing the natural ligand conjugated to an enzyme donor fragment of .beta.-galactosidase for competing with the sample compound for the natural acceptor binding site or in the absence of competition where the sample compound binds to an allosteric site. By adding the enzyme acceptor fragment of the .beta.-galactosidase and substrate, the binding affinity of the sample compound may be evaluated as a measure of agonist or antagonist capability.

Abstract: A method is described for the use of monoclonal antibodies in a sensitive immunoassay for halogenated dioxins and dibenzofurans in industrial samples which contain impurities. Appropriate sample preparation and selective enzyme amplification of the immunoassay sensitivity permits detection of dioxin contaminants in industrial or environmental samples at concentrations in the range of a few parts per trillion.

Abstract: Methods using an antibody having binding specificity to ouabain to immunologically measure the level of human ouabain in body fluid or tissue of a subject are disclosed.

Abstract: The subject invention provides an antigen characterized as having a molecular weight of approximately 68 kD, being reactive with autoantibodies associated with mental illness especially schizophrenia, being located in neuronal cells, and co-migrating with a protein band in SDS-PAGE which is recognized by rabbit antibodies which react with the peptide whose sequence is Ala-Lys-Xaa-Val-Lys-Phe-Gly-Ala-Asp-Ala-Xaa-Ala-Leu-Met-Leu (SEQ ID NO: 2). The invention also provides methods for detecting in a sample from a subject the presence of an antibody to the neuronal antigen, determining the propensity of a subject toward a psychiatric disease, diagnosing and treating a subject having mental illness.

Abstract: The present invention is directed toward the use of a synthetic peptide as the antigen in an immunoassay for the detection of antibodies against the equine infectious anemia virus in the serum of horses. The synthetic peptide corresponds to the amino acid sequence of an antigenic portion of the GP-45 envelope protein of the equine infectious anemia virus. The immunoassay may be a direct second antibody immunoassay, a one or two step sandwich immunoassay, or a competitive immunoassay.

Abstract: A process is disclosed for the determination of the malignant potential of a tumor. The process comprises the steps of determining the amount of BBO in a tumor sample by reacting the BBO in a tumor sample with a BBO-binding lectin or a BBO-specific antibody to form a BBO-lectin or a BBO-specific antibody complex. Then, the amount of BBO-lectin or BBO-antibody complex or of unreacted BBO can be measured.

Abstract: The present invention is directed to the measurement of soluble leukocyte surface markers, soluble T cell growth factor receptors, soluble complement receptors, soluble T cell differentiation antigens, or related soluble molecules or fragments thereof, and the use of such measurements in the diagnosis and therapy of diseases and disorders. The invention is also directed to the measurement of soluble CD35 (sCD35) or fragments thereof, and the use of such measurements in detecting disease or disorders. A polyclonal sandwich assay is provided for the detection and/or measurement of soluble CD35. The invention further relates to the measurement of total leukocyte markers or fragments thereof, and the use of such measurements in the detection and diagnosis of diseases or disorders. The term "total" leukocyte marker used herein refers to the total amount of a leukocyte marker in a sample, including that present in membrane and intracellular compartments and extracellular soluble compartments.

Abstract: A chemiluminescent reaction, which may be utilized as an immunoassay, carried out by 2,3-dihydro-1,4-phthalazinedione or its derivative, a peroxidase, and an oxidant, is enhanced by adding a phenolic compound such as (4-cyanomethylthio)phenol thereto. Especially, it is preferred that (4-cyanomethylthio)phenol is added to a mixture of luminol, horseradish peroxidase, and hydrogen peroxide to provide a significantly enhanced and stabilized luminescent reaction. Involving this enhanced luminescent reaction to an immunoassay, the sensitivity of the assay may be increased.

Abstract: This invention is directed to the identification, isolation and use of nonprostate derived markers, such as markers derived from the seminal vesicles, and antibodies which recognize these markers in the diagnosis of invasive proatic neoplasia, to diagnostic aids for screening biological samples for evidence of invasive prostatic neoplasia, and to methods for the use of these diagnostic aids.

Abstract: In a method of producing monoclonal antibodies against endothelial type plasminogen activator inhibitor and immunologically similar inhibitors myeloma cells are fused with antibody-producing cells obtained from mammals which have been immunized with said plasminogen activator inhibitor or with antibody-producing cells, which in vitro have been immunized with said plasminogen activator inhibitor and the hybridomas producing antibodies against the above mentioned inhibitor are selected. The antibody-producing cells are preferably spleen cells or lymph node cells, most preferably spleen cells, obtained from mice immunized with the above mentioned inhibitor.

Abstract: Immunodiagnostic tests in which enzymes or antibodies are bound to porous carrier materials can be carried out by employing as porous carrier materials macroporous polymer membranes which are prepared by(a) dispersing an insoluble filler in a solution which contains at least two incompatible polymers in amounts which lead to phase separation in the solution, resulting in a homogeneous casting solution, and(b) applying this solution to a support and carrying out a precipitation coagulation.

Abstract: The present invention contemplates a method for detecting contempory infection by H. pylori in a mammal comprising contacting a mucous secretion from said mammal with an antigen component from H. pylori for a time and under conditions sufficient for an IgG antibody in said mucous secretion specific to said antigen component to form a complex therewith and then subjecting said complex to a detecting means. Preferably, the antigen component is immobilized onto a solid support.

Abstract: The present invention provides an improved method for staining slides using immunochemical reagents. The method comprises the following steps. The assay region of a slide (the region containing the tissue section)is washed with an improved rinsing solution comprising water and a detergent. An evaporation inhibitor liquid is applied to the slide to cover the assay region. For antigens requiring unmasking, the tissue section is combined with an improved, stabilized proteolytic enzyme solution. The slide is rinsed, and the evaporation inhibitor liquid is reapplied to the slide. A primary antibody in an improved diluent containing globulins from the same species as a second antibody is combined with the tissue section for a time sufficient for substantially complete antibody binding. The slide is rinsed, and the evaporation inhibitor liquid is reapplied. A labeled second antibody in the improved diluent is combined with the tissue section for a time sufficient for substantially complete antibody binding.

Abstract: Methods and devices are provided for carrying out assays with minimal technical training where quantitative visual determinations may be made. The devices provide for a flow-path where a sample receiving element is moved from a sample receiving position to a position where it serves to bridge a transport element and a measurement element, so that the sample may be transported from the sample element to the measurement region. Labelled conjugates are provided which migrate a distance into the measurement region related to the amount of analyte in the sample.

Abstract: Methods and compositions are provided for the detection of analytes. The method employs a fluorescence production layer which comprises a fluorescent polymerized polyunsaturated lipid layer in association with a ligand which is a member of a specific binding pair, where the ligand is competitive with the analyte for the complementary binding member or is a complementary binding member. By providing for a fluorescence modulation reagent which binds to the fluorescence production layer in proportion to the amount of analyte in the sample, by measuring the resulting fluorescence after carrying out the assay methodology, the amount of analyte can be determined quantitatively.

Abstract: Methods and compositions are provided for determining the prognosis of human breast carcinoma through in vitro or in vivo detection of an antigen expressed and shed by cancer cells. The presence of this antigen is positively correlated with the presence of cancer and the number of cells expressing this antigen is correlated with a high incidence of tumor relapse, distant relapse and shortened relapse-free survival time.

Abstract: The invention concerns a method of homogeneous immunoassay of a ligand in a liquid test sample which comprises: a)incubating a mixture of (1) the liquid test sample; (1i) where the ligand under assay has only one epitope, a covalent conjugate of the ligand with any mono- or poly-epitope molecule having at least one epitope distinct from the epitope of the ligand; (2) a labile enzyme; (3) a first bispecific monoclonal antibody protecting the activity of the encyme through binding to a first epitope on the encyme and capable of binding the ligand under assay; and (4) a second bispecific monoclonal antibody capable of bonding said enzyme and a second distinct epitope on the ligand under assay or an epitope of the said covalent conjugate; whereby a quaternary immunocomplex is formed; b) after incubation, subjecting the mixture to conditions whereby any enzyme not present in such a quaternary immunocomplex is inactivated; and c) determining the amount of detectable encyme, the determination being related to the am

Abstract: The present invention relates to a novel method to identify compounds that inhibit proteolytic cleavage by dibasic amino acid processing endoproteases that includes contacting a yeast strain with a putative inhibitory compound under conditions in which, in the absence of the compound, the yeast strain can cleave a precursor protein having a dibasic amino acid processing site and determining if the putative inhibitory compound inhibits cleavage of the precursor protein. The present invention includes a method to identify compounds capable of inhibiting infectious agents, such as viruses, that depend upon dibasic amino acid processing endoprotease cleavage for propagation. The present invention also includes assay kits based on such a method.

Abstract: Low density lipoproteins are directly determined in fluid samples by selectively precipitating low density lipoproteins from the sample by forming clusters, selectively consuming the high density and very low density lipoproteins, and resolubilizing the low density lipoproteins for direct determination thereof. The clusters are formed by treating the fluid sample with a mixture of a polyanionic compound, a divalent metal, and a nucleating agent. The clusters are redissolved and assayed for low density lipoproteins.

Abstract: A process for identifying plasma samples containing effective antibody titers for the treatment and/or prophylaxis of infections caused by a respiratory virus. The process comprises contacting a plasma sample containing antibodies against a respiratory virus with the respiratory virus. The mixture of plasma sample and virus is then contacted with a plurality of cells. The remaining non-neutralized virus in the sample is then determined through an immunoassay following replication of the virus in the cells. Plasma samples which, at a preselected minimum antibody titer value, prevent viral replication in the cells, are then selected. Plasma from which the selected samples were derived are then pooled to provide an immunoglobulin preparation having increased effectiveness in the prophylaxis and/or treatment of infections caused by the respiratory virus.

Abstract: The present invention provides an improved buffer solution for conducting an immunological method for measuring apoprotein of human tissue factor, and a kit therefor.

Abstract: 2-methyl-4-hexene- and 3-methyl-5-heptene-l,2-diol derivatives are disclosed together with methods for preparing such derivatives. Where the derivative is a 2-methyl-4-nexene- or 3-methyl-5-heptene-l,2-diol conjugated to a label, the conjugates are useful in immunoassays. Where the 2-methyl-4-hexene or 3-methyl-5-heptene-l,2-diol is conjugated to an immunogenic carrier, the conjugates may be employed as an immunogen for use in the preparation of antibodies. The label conjugate and the antibodies can be utilized in an immunoassay for the determination or detection of cyclosporin in a sample suspected of containing cyclosporin.

Abstract: This invention relates to a substantially purified p100 which is a human neu related protein having a molecular weight in the range from about 97,000 daltons to about 115,000 daltons which corresponds substantially to the extracellular domain of the human neu gene product, said protein being detectable in a biological fluid.In another embodiment this invention relates to assays for detecting this protein.Finally, this invention also concerns monoclonal antibodies which are capable of binding to p100.

Abstract: A disposable diagnostic unit is provided which employs a housing which provides for a sample port, and a channel which feeds the sample to an incubation area by means of capillary action. The incubation area is underneath an optically-clear window and comprises a lipid membrane which has optical properties, particularly fluorescent properties and usually a reagent. A reservoir at the end of the channel downstream from the incubation area receives the sample and waste washes, while on one side of the platform area is a reagent reservoir and on the other side a side waste reservoir, so that one can move the reagent from the reagent reservoir through the platform area into the waste reservoir. Various reagents may be contained within the unit and the necessary liquids added automatically by appropriate instrumentation, so as to have the assay carried out automatically, without technician involvement, providing an accurate and sensitive determination.

Abstract: A method is described for diagnosing rheumatoid arthritis by providing a recombinant IgM-specific rheumatoid arthritis-associated antigen and detecting antibodies against the antigen in patient sera. Preliminary steps of making a cDNA library from polyadenylated RNA purified from human cells, selecting recombinants that express the antigen, recloning cDNA containing the antigen gene in a high level expression vector, expressing the antigen in transformed cells, and purifying the antigen are also described.

Abstract: A method of assay of antioxidant activity of a biological fluid, which comprises monitoring the change exerted by the sample on a progressing luminescent reaction.

Abstract: A method of detecting in a sample CTL specific for a particular virus, e.g. HIV, comprises contacting the sample with a support carrying immobilized antibodies to a surface antigen on T cells; separating the support and attached materials; contacting the separated support with target cells matched to the HLA type of the source of the sample and with HLA matched peptide epitope of the virus that interacts with the CTL of interest; and monitoring lysis of the target cells.